Effectiveness of Oximes 2-PAM and HI-6 in Recovery of Muscle Function Depressed by Organophosphate Agents in the Rat Hemidiaphragm: An in Vitro Study

Effectiveness of Oximes 2-PAM and HI-6 in Recovery of MuscleFunction Depressed by Organophosphate Agents in the Rat Hemidiaphragm:An in vitro Study. REDDY, V. K., DESHPANDE, S. S., CINTRA, W.M., SCOBLE, G. T., AND ALBUQUERQUE, E. X. (1991). Fundam. Appl.Toxicol. 17, 746–760. Phrenic nerve diaphragm musclesof young adult rats were used to study the ability of the oximes2-PAM and HI-6 to recover muscle function depressed by organophosphate(OP) agents. The single twitch of diaphragm muscles which wereexposed to soman (0.2 mm) recovered after washing with salinefor 3 hr, but the muscles pretreated with sarin (0.4 µM),VX (0.2 µM), or tabun (0.4 µM) showed only partialrecovery. In addition, after 3 hr washing, the muscles pretreatedwith soman as well as with tabun did not recover the tetanussustaining ability (TSA), yet complete recovery was observedwith muscles pretreated with sarin and VX. These results indicatethat the OPs have different effects on muscle contractile propertiesand that VX- and sarin-pretreated muscles recover equally wellafter wash with physiological solution. The recovery of twitchtension of diaphragm muscles by 2-PAM and HI-6 was similar tothat achieved by washing with saline for 3 hr for sarin- andsoman-exposed muscles. The most remarkable differences wereseen in the recovery of TSA. Both 2-PAM and HI-6 recovered theTSA of muscles that were pretreated with sarin and VX. Although2-PAM recovered the TSA after tabun pretreatment, HI-6 had nodiscernible effect. On the other hand, HI-6 recovered the TSAof soman-pretreated muscles but 2-PAM did not. The effectivenessof muscle function recovery was not related to the oximes' abilityto reactivate AChE, thus indicating that the recovery of musclecontractility may be attributed to a direct effect of thesecompounds on the muscle.